The present invention relates to a continuous or semicontinuous process for the preparation of coarse-particle dicalcium monohydrogen phosphate dihydrate from pure phosphoric acid and precipitated calcium carbonate. After appropriate drying, the products prepared by precipitation reactions are particularly suitable as carrier substances for direct tableting in the pharmaceutical industry.
Direct tableting is distinguished from conventional tableting methods in that the tablet mixture need not be subjected to any separate granulation process, for example, a wet or dry granulation, prior to pressing, in order to produce abrasion-resistant tablets having a long shelf life. Instead, the components can be pressed directly after the mixing procedures, resulting in a substantial saving of costs and time, as well as requiring less apparatus.
Dicalcium monohydrogen phosphate dihydrate (DCP dihydrate) is being used to an increasing extent as a carrier substance for direct tableting. For example, according to U.S. Pat. No. 3,134,719, unmilled DCP dihydrate having a coarse-particle structure is used effectively. It has been found that it is not sufficient simply to use unmilled, coarse-particle DCP dihydrate, but that, in order to achieve optimization and reproducibility in the compressive pressure/hardness properties, it is desirable to employ a DCP dihydrate having a certain particle structure (particle size and crystal shape). Regarding the particle size, the particle size in the range between about 63 and 450 .mu.m, preferably between about 90 and 300 .mu.m, has proven particularly suitable. In order to achieve optimum flow behavior, the crystal shape should be virtually spherical.
The essential precondition for a product suitable for direct tableting is fulfilled only when these two criteria are both met at the same time. Moreover, it is of course essential to meet the purity requirements (for example, heavy metal content, impurities) of the relevant pharmacopoeia.
DCP dihydrate is prepared in many places according to the prior art by conventional methods, for example, by reacting sodium phosphate with a calcium chloride solution (cf. Ullmanns Enzyklopeadie der technischen Chemie, 4th edition, volume 18, page 334, Weinheim 1979). However, the products prepared in this manner are generally so finely crystalline that they cannot be used for direct tableting. Although, under advantageous conditions, the fines (&lt;75 .mu.m), after appropriate compacting and comminution, for example, according to European Pat. No. 54,333, can also be used for tableting purposes; however, the procedure entails additional process steps and costs.